University of Illinois Urbana-Champaign

Interactions of Anticancer Drugs With DNA Studied by High-Resolution NMR Spectroscopy

Lian, Chenyang

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Description

Title
Interactions of Anticancer Drugs With DNA Studied by High-Resolution NMR Spectroscopy
Author(s)
Lian, Chenyang
Issue Date
1997
Doctoral Committee Chair(s)
Wang, Andrew H.J.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Molecular
Language
eng
Abstract
The anthracycline daunorubicin has been widely used to treat acute leukemia clinically. The newly designed bisanthracycline bisintercalator WP631 has shown promising results against the anthracycline resistance that is due to the transport proteins, e.g., P-glycoprotein. The 3D structures of 1:1 WP631/d(CGTACG)$\sb2$ and 1:1 WP631/d(CGJACG)$\sb2$ showed that the aglycone rings intercalate slightly shallower than those in the 2:1 DAU/d(CGTACG)$\sb2$ and the daunosamine moieties are elevated from the minor groove floor, which would explain why the binding constant of WP631 to DNA is 3 orders less than expected. WP631 has also shown tight binding to modified DNA d(CGJACG)$\sb2.$ The 3D structures of these two complexes have pointed the direction for the future design of bisanthracycline drugs.
Graduation Semester
1997
Type of Resource
text
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http://hdl.handle.net/2142/84367

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